Phylogenetics studies the connections among genetic material to better understand how biological entities evolved. In this case, researchers tracked the genetic differences between the various HIV viruses to determine which viruses' genes were extremely similar. These viruses probably evolved from a common "ancestor," which means that participants with such genetically similar HIV versions likely were in close contact with each other. Phylogenetic tracing thus allows researchers to group people living with HIV into "transmission clusters" -- groups with highly similar HIV who likely transmitted or acquired the virus within that cluster. Many of these clusters include only two people, but some are bigger.

Study authors analyzed data from San Francisco, Calif., residents who were diagnosed with HIV between 2000 and 2015, received care at public facilities and for whom viral pol sequences were available. Viral pol sequences are chains of proteins in the pol region of the HIV virus that can be used to trace the genetic similarity between viruses. Records for 5,200 people had such sequences, and 275 of the records indicated that the person was a transgender woman.

Additional questions on a standard questionnaire asked about intravenous drug use and other activities that carry a risk for acquiring HIV, as well as sexual identity and sexual orientation. Many of the transgender women's viruses were not genetically similar to that of anyone else in the study; that is, they had acquired HIV from someone who was not participating in this study. However, the phylogenetic characteristics of 86 transgender women's HIV placed them in one or more of the transmission clusters. Overall, researchers identified 563 transmission clusters, 70 of which included transgender women. These 70 clusters and 86 women were the focus of the study.

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Traditionally, men who have sex with transgender women have been classified as MSM, Truong said. When that assumption was used to analyze the 70 transmission clusters, almost half of the groups included MSM who use injection drugs (IDU) and a quarter included non-MSM (transgender and cisgender women) who inject drugs. Furthermore, almost half of the transgender women in the study reported using injection drugs. Thus, there is a "high potential for HIV transmission between transgender women and injection drug users," researchers noted. More than half of the clusters included MSM who do not inject drugs, and only 1% of the groups had heterosexual men.

However, when the data were re-analyzed assuming that men who have sex with transgender women are not MSM if their cluster does not include other men, only 16% of clusters included MSM who inject drugs, and the same percentage had MSM who do not use injection drugs. The proportion of clusters that included heterosexual men jumped to almost half, and non-MSM IDUs were in almost 60% of clusters.

Researchers then analyzed 130 transmission clusters that included cisgender women and found the proportions of groups that included MSM or heterosexual men to be similar to the scenario in which male partners of transgender women are not assumed to be MSM. They concluded that classifying men who have sex with transgender women as MSM "may obscure [transgender women's] true sexual networks." As a result, HIV prevention programs targeted at MSM may not apply to transgender women or their sexual partners, they added.

Study results show that there may be a hidden group of heterosexual men who have sex with transgender women, Gus Cairns noted in the aidsmap article. That fact raises two questions, he added: Are these men at higher risk of seroconversion, and do they represent a risk factor for cisgender women with whom they might also have sex? The San Francisco Department of Public Health is hoping to address the question of transgender women's sexual partners soon, Erin Wilson, Dr.P.H., announced during the question and answer period of the IAS presentation. Authors of the current study are also working on a similar phylogenetic analysis of transgender women's male sexual partners, Truong said.

She added that the impetus for this study came from the fact that there is a persistent incidence of HIV among cisgender women in San Francisco, even though most seroconversions are among supposed MSM. Study result show that some heterosexual men may have been mislabeled MSM, which might account for this seeming paradox, she said.

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